The objective of the proposed investigation is to make a detailed biochemical and immunological study of the type-common envelope glycoprotein gD of herpes simplex virus (HSV) type 1 (oral form) and type 2 (genital form). Glycoprotein gD plays an important role in the initial stages of HSV-1 and HSV-2 infection as evidenced by the fact that antisera directed against this protein neutralize virus infectivity. A library of monoclonal antibodies comprising 4 groups, will be utilized to probe the structure of gD from HSV-1 (gD-1) and gD from HSV-2 (gD-2). Competition binding assays will be performed to determine the number of distinct epitopes recognized by the monoclonal antibodies. Proteolytic enzymes will be used to dissect the native glycoproteins bound to specific monoclonal antibodies. Fragments of gD-1 and gD-2 retaining antigenic activity will be isolated and characterized by tryptic peptide and amino acid analysis. Intertypic recombinants will be examined by tryptic peptide analysis in order to confirm the genomic map position of gD. Evidence for intragenic recombination of gD will be sought and the antigenic structure of these recombinants will be compared with that of gD-1 and gD-2. The chemical composition of gD-1 and gD-2 will be determined. These studies will include: amino acid analysis, carbohydrate analysis and sequencing of N-terminal amino acids. The studies proposed in this grant have the potential to lead in two important future directions: 1. elucidation of the primary structure of gD and an understanding of its synthesis and regulation and 2. the application of gD and its antigenically active fragments to studies of the immune response to HSV.